Methanesulfonyl chloride → HCID 44198415, compound

Participants

Reaction Conditions

Reaction Steps

The title compound was prepared by the route outlined in Scheme 8, following the same experimental procedures as for Example 51, with the following modification. Deprotection of intermediate (8e), 5-(tert-Butyl-dimethyl-silanyloxymethyl)-2-[5-{[1-(4-methyl-benzyl)-1H-pyrazole-4-carbonyl]-amino}-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]-indole-1-carboxylic acid tert-butyl ester, in the usual manner, yielded 2-[5-[(1-benzyl-1H-pyrazole-4-carbonyl)-amino]-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]-5-hydroxymethyl-indole-1-carboxylic acid tert-butyl ester. DIPEA (153 μL, 0.9 mmol) and 2-[5-[(1-benzyl-1H-pyrazole-4-carbonyl)-amino]-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]-5-hydroxymethyl-indole-1-carboxylic acid tert-butyl ester (0.2 g, 0.3 mmol) were stirred in 1,2-dichloroethane (5 mL) and cooled to 0° C. Methanesulfonyl chloride (27 μL, 0.36 mmol) was added drop wise at 0° C. and stirred for a further 2 hours at 0° C. cis-2,6-Dimethylpiperidine (118 μL 0.9 mmol) was added drop wise at 0° C. and then the reaction was allowed to attain ambient temperature. The reaction mixture was heated at reflux overnight followed by cooling to ambient temperature. The reaction mixture was diluted with ethyl acetate (30 mL), washed with water (30 mL), saturated sodium hydrogen carbonate solution (30 mL), brine, dried (Na2SO4) and concentrated in vacuo. The resultant crude product was taken up in methanol (1 mL) and loaded onto a 5 g SCX column. The column was flushed with methanol and then eluted with ammonia solution 7N in methanol. The eluent was concentrated in vacuo to afford the title compound as a light brown solid, 120 mg, 53%.

Provenance & Evidence